Clinical Outcome and 7-Day Virological Clearance in High-Risk Patients with Mild-Moderate COVID-19 Treated with Molnupiravir, Nirmatrelvir/Ritonavir, or Remdesivir.

INTRODUCTION: We compared the effectiveness and virological clearance (VC) at day 7 (T7) post-treatment with molnupiravir, nirmatrelvir/ritonavir, and remdesivir in SARS-CoV-2-infected patients at high risk (HR) for clinical progression. METHODS: We conducted a retrospective study enrolling HR patients with mild-to-moderate COVID-19 (Jan-Oct 2022) treated with nirmatrelvir/ritonavir or molnupiravir or 3 days of remdesivir. We investigated clinical recovery at T7 (resolution of symptoms for ≥ 72 h or all-cause death), VC at T7 (PCR/antigenic negative nasopharyngeal swab), and median time to VC (days from symptom onset to the first negative swab). Factors associated with VC were investigated by logistic regression. RESULTS: In the study, 92/376 (43.8%) patients received molnupiravir, 150/376 (24.7%) nirmatrelvir/ritonavir, and 134/376 (31.5%) remdesivir. Forty-nine (13%) patients were unvaccinated or incompletely vaccinated. Patients treated with nirmatrelvir/ritonavir were younger and presented immunodeficiencies more frequently; remdesivir was used more commonly in patients hospitalized for other diseases. A high proportion of patients obtained clinical recovery without differences among the therapies (97.5% for molnupiravir, 98.3% for nirmatrelvir/ritonavir, and 93.6% for remdesivir); 12 (3.7%) patients died. Nirmatrelvir/ritonavir was associated with a higher proportion of T7 VC and a shorter time to VC compared to molnupiravir/remdesivir, also after adjustment for age and immunodeficiency (AOR 0.445 RDV vs. NMV-r, 95% CI 0.240-0.826, p = 0.010; AOR 0.222 MNP vs. NMV-r, 95% CI 0.105-0.472, p < 0.001). CONCLUSIONS: SARS-COV-2 antiviral treatments are an excellent therapeutic strategy in HR patients. Nirmatrelvir/ritonavir showed a higher proportion of VC as early as 7 days after treatment, confirming its likely superiority in indirect comparisons.

Nirmatrelvir-ritonavir, molnupiravir, and a 3-day course of remdesivir are antiviral therapies recommended in patients with a mild-to-moderate COVID-19 disease at high risk of clinical progression. Randomized controlled trials and observational studies have shown their efficacy in reducing all-cause mortality and clinical progression. Few data are available about a direct comparison among the three drugs; furthermore, the possible role of nirmatrelvir-ritonavir in increasing viral clearance and in reducing the duration of viral shedding needs to be further elucidated. We thus investigated the effectiveness, safety, and virological clearance 7 days after treatment with these three antivirals in our retrospective cohort. We included in the analysis patients that have received these treatments from January 2022 and October 2022; we observed that patients receiving nirmatrelvir-ritonavir displayed a shorter median time from symptoms' onset to virological clearance and a higher proportion of virological clearance at day 7, also after adjustment for possible confounders, compared to molnupiravir and remdesivir. Our data might help in understanding which COVID-19 patients may benefit mostly from antiviral therapies and in the choice of antiviral therapy.

HIV-Related Oral Mucosa Lesions: A Cross-Sectional Study on a Cohort of Italian Patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection can be associated with oral mucosal diseases, including oral candidiasis and HPV infection, which are putative indicators of the immune status. AIM AND METHODS: This retrospective cross-sectional study was aimed at assessing the prevalence of HIV-related oral mucosal lesions in a cohort of Italian HIV+ patients regularly attending the Clinics of Infectious Diseases. RESULTS: One hundred seventy-seven (n = 177) patients were enrolled and 30 (16.9%) of them showed HIV-related diseases of the oral mucosa. They were mainly found in male patients over 35 years old, undergoing Combination Antiretroviral Therapy (cART), and with CD4+ count < 500/µL. Oral candidiasis was the most common HIV-related oral lesion. No significant correlations could be detected between the prevalence of HPV infection and other clinical parameters (lymphocyte count, cART treatment and viral load). CONCLUSIONS: HIV-related oral mucosal diseases can correlate with immunosuppression. Early diagnosis and management of oral lesions in HIV+ patients should be part of the regular follow-up, from a multidisciplinary perspective of collaboration between oral medicine and infectious disease specialists, in an attempt to reduce morbidity due to oral lesions and modulate antiretroviral therapy according to the patient's immune status.

A No-History Multi-Formula Approach to Improve the IOL Power Calculation after Laser Refractive Surgery: Preliminary Results.

This retrospective comparative study proposes a multi-formula approach by comparing no-history IOL power calculation methods after myopic laser-refractive-surgery (LRS). One-hundred-thirty-two eyes of 132 patients who had myopic-LRS and cataract surgery were examined. ALMA, Barrett True-K (TK), Ferrara, Jin, Kim, Latkany and Shammas methods were evaluated in order to back-calculate refractive prediction error (PE). To eliminate any systematic error, constant optimization through zeroing-out the mean error (ME) was performed for each formula. Median absolute error (MedAE) and percentage of eyes within ±0.50 and ±1.00 diopters (D) of PE were analyzed. PEs were plotted with corresponding mean keratometry (K), axial length (AL), and AL/K ratio; then, different ranges were evaluated. With optimized constants through zeroing-out ME (90 eyes), ALMA was better when K ≤ 38.00 D-AL > 28.00 mm and when 38.00 D < K ≤ 40.00 D-26.50 mm < AL ≤ 29.50 mm; Barrett-TK was better when K ≤ 38.00 D-AL ≤ 26.50 mm and when K > 40.00 D-AL ≤ 28.00 mm or AL > 29.50 mm; and both ALMA and Barrett-TK were better in other ranges. (p < 0.05) Without modified constants (132 eyes), ALMA was better when K > 38.00 D-AL ≤ 29.50 mm and when 36.00 < K ≤ 38.00 D-AL ≤ 26.50 mm; Barrett-TK was better when K ≤ 36.00 D and when K ≤ 38.00 D with AL > 29.50 mm; and both ALMA and Barrett-TK were better in other ranges (p < 0.05). A multi-formula approach, according to different ranges of K and AL, could improve refractive outcomes in post-myopic-LRS eyes.

HIV-Indicator Condition Guided Testing in a Hospital Setting.

Late diagnosis is still a major issue in HIV infection management, leading to important consequences for both patients and community. In this perspective, HIV screening targeted on some clinical conditions (HIV indicator conditions-HIVICs) emerged as a useful strategy, also involving patients not considered at high behavioral risk. We organized an in-hospital HIVICs guided screening campaign named ICEBERG in Milan, Italy, between 2019 and 2021. Among the 520 subjects enrolled, mainly presenting with viral hepatitis or mononucleosis-like syndrome, 20 resulted HIV positive (3.8% prevalence). A significant proportion of them had multiple conditions and advanced immunosuppression, with 40% being AIDS-presenters. As adherence to the screening campaign was modest for non-ID specialists, educational interventions to raise clinicians' sensitivity are urgently needed. HIV-ICs guided testing was confirmed as a useful tool, but a combined approach with other screening strategies seems to be essential for early HIV diagnosis.

The timeline of non-vocal and vocal communicative skills in infants with hearing loss.

Objective: The study investigates what is the link between early verbal and non-vocal abilities, when does predominantly verbal communicative style occur after the intervention with cochlear implants (CI) or hearing aids (HA), and how predictive it is of later linguistic development in deaf and hard of hearing (DHH) infants and children. Methods: Cohort: children with moderate-to-profound hearing impairment (N = 49, 20 girls, mean age at HA or CI intervention = 15 months, range: 4-35 months). Measures: Receptive and productive vocabulary at 24 and 36 months and video analysis at 12 months post-intervention. Analysis: Predictive values of total and verbal responses to communicative turns for later vocabulary development were assessed, as well as the relative time course of the development of vocal/verbal communication in DHH children. Results: Vocabulary at 24 months is predicted by auditory responses at 12 months, as well as by overall responsiveness before intervention. Non-vocal responses decline and overall verbal responses increase significantly between 6 and 12 months after intervention. The trend is delayed in children with delayed (>12 months of age) treatment with CI or HA. Conclusions: Age of intervention affects the development of vocal/verbal communicative style. Language development, in particular, vocabulary growth, can be further stimulated by the enhancement of preverbal (both vocal and non-vocal) communicative skills.

Pareto Optimality in Multilayer Network Growth.

We model the formation of multilayer transportation networks as a multiobjective optimization process, where service providers compete for passengers, and the creation of routes is determined by a multiobjective cost function encoding a trade-off between efficiency and competition. The resulting model reproduces well real-world systems as diverse as airplane, train, and bus networks, thus suggesting that such systems are indeed compatible with the proposed local optimization mechanisms. In the specific case of airline transportation systems, we show that the networks of routes operated by each company are placed very close to the theoretical Pareto front in the efficiency-competition plane, and that most of the largest carriers of a continent belong to the corresponding Pareto front. Our results shed light on the fundamental role played by multiobjective optimization principles in shaping the structure of large-scale multilayer transportation systems, and provide novel insights to service providers on the strategies for the smart selection of novel routes.

The Effects of Glucose Therapy Agents-Apple Juice, Orange Juice, and Cola-on Enteral Tube Flow and Patency.

To develop evidence-based hypoglycemia treatment protocols in patients receiving total enteral nutrition, this study determined the effect on enteral tube flow of glucose therapy agents: apple juice, orange juice, and cola, and it also examined the effects of tube type and feed type with these glucose therapy agents. For this study, 12 gastrostomy tubes (6 polyethylene and 6 silicone) were set at 50 mL/h. Each feeding set was filled with Isosource HN with fibre or Novasource Renal. Each tube was irrigated with 1 glucose therapy agent, providing approximately 20 g of carbohydrate every 4 h. Flow-rate measurements were collected at 2 h intervals. The results showed that the glucose therapy agent choice affected flow rates: apple juice and cola had higher average flow rates than orange juice (P = 0.01). A significant difference was found between tube type and enteral formula: polyethylene tubes had higher average flow rates than silicone tubes (P < 0.0001), and Isosource HN with fibre had higher flow rates than Novasource Renal (P = 0.01). We concluded that apple juice and cola have less tube clogging potential than orange juice, and thus may be considered as primary treatment options for hypoglycemia in enterally fed patients. Polyethylene tubes and Isosource HN with fibre were less likely to clog than silicone tubes and Novasource Renal.

Pareto Optimal Design for Synthetic Biology.

Recent advances in synthetic biology call for robust, flexible and efficient in silico optimization methodologies. We present a Pareto design approach for the bi-level optimization problem associated to the overproduction of specific metabolites in Escherichia coli. Our method efficiently explores the high dimensional genetic manipulation space, finding a number of trade-offs between synthetic and biological objectives, hence furnishing a deeper biological insight to the addressed problem and important results for industrial purposes. We demonstrate the computational capabilities of our Pareto-oriented approach comparing it with state-of-the-art heuristics in the overproduction problems of i) 1,4-butanediol, ii) myristoyl-CoA, i ii) malonyl-CoA , iv) acetate and v) succinate. We show that our algorithms are able to gracefully adapt and scale to more complex models and more biologically-relevant simulations of the genetic manipulations allowed. The Results obtained for 1,4-butanediol overproduction significantly outperform results previously obtained, in terms of 1,4-butanediol to biomass formation ratio and knock-out costs. In particular overproduction percentage is of +662.7%, from 1.425 mmolh⁻¹gDW⁻¹ (wild type) to 10.869 mmolh⁻¹gDW⁻¹, with a knockout cost of 6. Whereas, Pareto-optimal designs we have found in fatty acid optimizations strictly dominate the ones obtained by the other methodologies, e.g., biomass and myristoyl-CoA exportation improvement of +21.43% (0.17 h⁻¹) and +5.19% (1.62 mmolh⁻¹gDW⁻¹), respectively. Furthermore CPU time required by our heuristic approach is more than halved. Finally we implement pathway oriented sensitivity analysis, epsilon-dominance analysis and robustness analysis to enhance our biological understanding of the problem and to improve the optimization algorithm capabilities.

Consulta de enfermagem geriátrica e gerontológica: uma necessidade / Geriatric and gerontologic nursing consultation: one necessity

As autoras descrevem, a partir da pesquisa bibliográfica, conceitos sobre consulta de enfermagem e a importância de sua aplicaçäo em Geriatria e Gerontologia. A seguir apresentam os itens que devem conter uma consulta de enfermagem Geriátrica e Gerontológica.